Maternal Meiotic Drive of Mouse Chromosome 11

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DESCRIPTION (provided by applicant): Mendel's law of equal transmission of the two alternative forms of a gene that are carried by each individual is nearly universal. The fact that the two forms of each gene are each transmitted to one-half of an individual's offspring in almost all cases indicates that there are few instances in which the "fairness" of meiosis is compromised. We have uncovered an example of "unfair meiosis" in female mice (called maternal meiotic drive) that results in the, preferential transmission of a gene that causes early embryo lethality in the following generation. We propose that the mechanism by which this occurs involves the formation of an additional "egg attachment site" on the chromosome that carries the embryonic lethal gene. This additional site makes it twice as likely that the chromosome carrying the lethal gene will be transmitted to the egg (and, correspondingly only half as likely that the chromosome carrying the other form of the gene will be transmitted to the egg). We plan to identify this attachment site, at the molecular level, determine how it is created and what genes are involved in its creation. The ability to control the activity of such sites may allow one to manipulate the frequency with which some traits are inherited. In addition, this example of "unfair meiosis" in females has a unique component because the onset of "unfair meiosis" in the egg is brought about by a gene or gene product provided by the sperm. We propose to identify this paternal gene and determine how it is able to influence the segregation of chromosomes in the egg.